Continuous beta cell cultures are needed for quantitative controlled experiments to a) elucidate the mechanisms of insulin biosynthesis and secretion; b) evaluate the immunological characteristics of beta cell constituents; and c) determine the mechanisms whereby specific cytotoxic chemicals and viruses damage beta cells selectively. Long-term maintenance, continuous passage, and the bulk propagation of pancreatic islet cells cells "in vitro" have been hampered thus far by the limited replicative ability of the normal beta cell. We are establishing reproducible animal models for induction of hyperplasia and transformation of the beta cell to establish permanent lines of insulin-producing lines of insulin-producing cells in tissue culture. Weanling rats and inbred mice receive injections of cortisone and gold-thioglucose to induce hyperplasia of the beta cells. Rodents than are administered ionizing irradiation and streptozotocin-nicotinamide. To detect hyperplastic and neoplastic changes in beta cells, blood from treated animals is monitored at intervals for glucose and assessed by radioimmunoasssay for elevated levels of insulin. Hyperplastic and transformed islet cells are isolated selectively using 1) differential attachment, 2) affinity columns, and 3) colloidal silica density gradients. Stimulation and establishment of beta cell lines is encouraged in vitro by use of complex media containing inhibitors for fibroblasts. The identification and assessment of the functional status of cultured beta cells is accomplished by aldehyde thionin and immunoperoxidase staining, transmission electron microscopy.